A new Conus peptide ligand for Ca channel subtypes

Abstract

A cDNA clone encoding a new ω-conotoxin was identified from Conus magus. The predicted peptide was chemically synthesized using a novel strategy that efficiently yielded the biologically active disulfide-bonded isomer. This peptide, ω-conotoxin MVIID, targets other voltage-gated calcium channels besides the N-subtype and exhibits greater discrimination against the N-channel subtype than any other ω-conotoxin variant to date. Consequently, ω-conotoxin MVIID may be a particularly useful ligand for calcium channel subtypes that are not of the L- or N-subclasses. Of the eight major sequence variants of ω-conotoxins that have been elucidated, four come from Conus magus venom. We suggest that sequence variants from the same venom may be designed to optimally interact with different molecular variants of calcium channels; such ω-conotoxin sets from a single venom may therefore be useful for helping to identify novel calcium channel subtypes.